Angiotensin receptor

Structure

The AT₁ and AT₂ receptors share a sequence identity of ~30%, but have a similar affinity for angiotensin II, which is their main ligand.

AT1

The AT₁ receptor is the best elucidated angiotensin receptor.

Location within the body

The AT1 subtype is found in the heart, blood vessels, kidney, adrenal cortex, lung and brain and mediates the vasoconstrictor effects.

Mechanism

The angiotensin receptor is activated by the vasoconstricting peptide angiotensin II. The activated receptor in turn couples to G_q/11 and G_i/o and thus activates phospholipase C and increases the cytosolic Ca²⁺ concentrations, which in turn triggers cellular responses such as stimulation of protein kinase C. Activated receptor also inhibits adenylate cyclase and activates various tyrosine kinases.

Effects

Effects mediated by the AT₁ receptor include vasoconstriction, aldosterone synthesis and secretion, increased vasopressin secretion, cardiac hypertrophy, augmentation of peripheral noradrenergic activity, vascular smooth muscle cells proliferation, decreased renal blood flow, renal renin inhibition, renal tubular sodium reuptake, modulation of central sympathetic nervous system activity, cardiac contractility, central osmocontrol and extracellular matrix formation.

AT2

AT₂ receptors are more plentiful in the fetus and neonate. The AT₂ receptor remains enigmatic and controversial – is probably involved in vascular growth. Effects mediated by the AT₂ receptor are suggested to include inhibition of cell growth, fetal tissue development, modulation of extracellular matrix, neuronal regeneration, apoptosis, cellular differentiation, and maybe vasodilation and left ventricular hypertrophy.

AT3 and AT4

Other poorly characterized subtypes include the AT₃ and AT₄ receptors. The AT₄ receptor is activated by the angiotensin II metabolite angiotensin IV, and may play a role in regulation of the CNS extracellular matrix, as well as modulation of oxytocin release.